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991.
Association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men 总被引:8,自引:0,他引:8
Fink HA Ewing SK Ensrud KE Barrett-Connor E Taylor BC Cauley JA Orwoll ES 《The Journal of clinical endocrinology and metabolism》2006,91(10):3908-3915
CONTEXT: The clinical value of measuring testosterone and estradiol in older men with osteoporosis and of measuring bone mineral density (BMD) in older men with testosterone or estradiol deficiency is uncertain. OBJECTIVE: The objective of the study was to examine the association of testosterone and estradiol deficiency with osteoporosis and rapid bone loss in older men. DESIGN: This study was a cross-sectional and longitudinal analysis. Setting: The study was conducted at six U.S. centers of the Osteoporotic Fractures in Men study. PARTICIPANTS: The study population consisted of 2447 community-dwelling men aged 65 yr or older. MAIN OUTCOME MEASURES: Total testosterone deficiency was defined as less than 200 ng/dl. Total estradiol deficiency was defined as less than 10 pg/ml. Osteoporosis was defined as femoral neck or total hip BMD T-score of -2.5 or less. Rapid bone loss was defined as 3%/yr or more. RESULTS: Prevalence of osteoporosis in men with deficient and normal total testosterone was 12.3 and 6.0% (P = 0.003) and 15.4 and 2.8% (P < 0.0001) in those with deficient and normal total estradiol. Among osteoporotic men and those with normal BMD, prevalence of total testosterone deficiency was 6.9 and 3.2% (P = 0.01), and prevalence of total estradiol deficiency was 9.2 and 2.4% (P = 0.0001). Incidence of rapid hip bone loss in men with deficient and normal total testosterone was 22.5 and 8.6% (p = 0.007) and in those with deficient and normal total estradiol was 14.3 and 6.3% (p = 0.08). CONCLUSIONS: Older men with total testosterone or estradiol deficiency were more likely to be osteoporotic. Those with osteoporosis were more likely to be total testosterone or estradiol deficient. Rapid hip bone loss was more likely in men with total testosterone deficiency. BMD testing of older men with sex steroid deficiency may be clinically warranted. 相似文献
992.
993.
Hale JS Boursalian TE Turk GL Fink PJ 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(22):8447-8452
Using GFP to mark recent thymic emigrants (RTEs) in mice carrying a GFP transgene driven by the recombination-activating gene 2 promoter, we demonstrate that RTEs are readily detectable even in 2-year-old mice, despite the fact that the proportion of the peripheral T cell pool comprised of RTEs declines with age. Although the number of RTEs decreases after reaching a peak at 6 weeks of age, thymic output as a function of thymic size is surprisingly age-independent. The CD4:CD8 ratio of RTEs declines with age, partly because of a striking decrease in steady-state proliferation of CD4+ RTEs in older mice. RTEs in aged mice undergo phenotypic maturation in the lymphoid periphery with delayed kinetics compared with young mice. RTEs from aged mice secrete less IL-2, proliferate less well, and achieve only weak expression of early-activation markers compared with more mature na?ve peripheral T cells from the same mice. The proportion of GFP- cells in the CD4+ and CD8+ thymic compartments increases with age, partly as a result of leakiness in the aged thymus, allowing reentry of na?ve peripheral T cells. 相似文献
994.
Neocortical neurogenesis in humans is restricted to development 总被引:6,自引:0,他引:6
Bhardwaj RD Curtis MA Spalding KL Buchholz BA Fink D Björk-Eriksson T Nordborg C Gage FH Druid H Eriksson PS Frisén J 《Proceedings of the National Academy of Sciences of the United States of America》2006,103(33):12564-12568
Stem cells generate neurons in discrete regions in the postnatal mammalian brain. However, the extent of neurogenesis in the adult human brain has been difficult to establish. We have taken advantage of the integration of (14)C, generated by nuclear bomb tests during the Cold War, in DNA to establish the age of neurons in the major areas of the human cerebral neocortex. Together with the analysis of the neocortex from patients who received BrdU, which integrates in the DNA of dividing cells, our results demonstrate that, whereas nonneuronal cells turn over, neurons in the human cerebral neocortex are not generated in adulthood at detectable levels but are generated perinatally. 相似文献
995.
Fink SR Smoley SA Stockero KJ Paternoster SF Thorland EC Van Dyke DL Shanafelt TD Zent CS Call TG Kay NE Dewald GW 《Cancer Genetics and Cytogenetics》2006,167(2):177-181
Loss of tumor protein 53 (TP53) has been associated with aggressive disease and poor response to therapy in B-cell chronic lymphocytic leukemia (B-CLL). TP53 is located at chromosome band 17p13 and its absence can be detected by fluorescence in situ hybridization (FISH) in the interphase nuclei of 8-10% patients with B-CLL. To study the cytogenetic mechanism for loss of TP53, metaphase and interphase FISH studies were conducted on 16 B-CLL patients to investigate 17p10 to 17p12, a chromosome region known to be rich in low-copy DNA repeats. Loss of TP53 was caused by an isochromosome with breakpoints between 17p10 and 17p11.2 in four patients, an unbalanced translocation involving 17p10 to 17p11.2 in nine patients, and an unbalanced translocation involving 17p11.2 to 17p12 in three patients. These findings indicate that loss of TP53 results from the absence of nearly the entire chromosome 17 p-arm rather than to monosomy 17 or deletions of TP53. Translocations or isochromosome formations at sites of low-copy DNA repeats in 17p10 to 17p12 appear to be the mechanism for the loss of TP53 in B-CLL. 相似文献
996.
997.
Szasz T Linder AE Davis RP Burnett R Fink GD Watts SW 《Journal of cardiovascular pharmacology》2010,56(6):627-634
Reactive oxygen species play an important role in the pathogenesis of hypertension, disease in which reactive oxygen species levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a reactive oxygen species-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on blood pressure have yielded controversial results. We hypothesized that XO inhibition would decrease blood pressure or attenuate the development of deoxycorticosterone acetate (DOCA)-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg per day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by high-performance liquid chromatography measurements of XO metabolites in urine, serum, and tissues demonstrating a decrease in products, increase in substrates, and detection of the active metabolite of allopurinol, oxypurinol. We monitored blood pressure continuously through radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model. 相似文献
998.
Disperse dyes, which are suitable for dyeing synthetic fibres, are responsible for the great majority of allergic contact
dermatitis (ACD) cases to textile dyes. The aim of the present study was to investigate the sensitising potential of various
disperse dyes using a biphasic protocol of the local lymph node assay (LLNA). Briefly, mice were shaved over a surface of
approximately 2 cm2 on their backs and treated using a “sensitisation-challenge protocol”. The shaved surface was treated once daily on days
1–3 with 50 μl of the test solution. Animals remained untreated on days 4–14. On days 15–17, mice were treated with 25 μl
of the test solution on the dorsum of both ears. Mice were killed on day 19 with deep CO2 anaesthesia, the lymph nodes prepared and various end points, such as ear thickness, ear punch weight, lymph node weight,
lymph node cell count and the proportion of various lymphocyte subpopulations, were determined by flow cytometry. The results
were compared to control group treated with the vehicle alone. Our results showed that almost all of the tested textile dyes
caused a significant increase in lymph node cell count and lymph node weight. We also observed an increase in ear thickness
and ear punch weight in most of the concentrations tested for various textile dyes. We observed a decrease in CD4+ and CD8+
cells and an increase in CD19+, CD45+ and CD45+/1A+ cells in most of the cases, which is characteristic for allergens. The
CD4+/CD69+ cells increased in only few experiments mainly with Disperse Blue 124 and Disperse Blue 106. Based on our results,
the disperse dyes could be arranged in four groups on the basis of their sensitising potency in the following decreasing order
(in parenthesis: lowest concentration causing a significant increase in lymph node cell number): group 1, strong: Disperse
Blue 124 and Disperse Blue 106 (0.003%); group 2, moderate: Disperse Red 1 and Disperse Blue 1 (3%); group 3, weak: Disperse
Orange 37 and Disperse Blue 35 (10%); and group 4, very weak: Disperse yellow 3 and Disperse Orange 3 (increase at 30% or
no increase at 30%). In conclusion, our study shows that the biphasic LLNA protocol was proficient enough to study the sensitisation
potential of tested textile dyes and provides data allowing to discriminate them according to their potency. 相似文献
999.
Hierarchically organized figures (for example, a large E made up of smaller N's) are frequently used to investigate directed and divided attention. Investigations of neurological and psychiatric patients, and also tachistoscopic and functional neuroimaging studies on healthy subjects, typically find the right hemisphere to be specialized for the processing of global stimuli and the left hemisphere to be specialized for the processing of local stimuli. In the current study, a group of 12 patients with visuo-spatial neglect (NP) after right hemisphere lesions and 12 age and sex-matched control subjects (CO) performed a directed and a divided attention task with hierarchically organized letters. As expected, faster reaction times were found for control subjects than for neglect patients, especially for the directed global attention task. Lower error rates were found for CO and NP for local than for global targets during the divided attention condition. Local on global interference was found for both groups in reaction times. These local processing advantages for older healthy adults have been reported previously. Additionally, an impairment in the divided attention task was found in both groups, but especially for global targets in NP. This impairment is consistent with other evidence of difficulty in disengaging attention shown by patients with visuo-spatial neglect. 相似文献
1000.
Schilbach L Wohlschlaeger AM Kraemer NC Newen A Shah NJ Fink GR Vogeley K 《Neuropsychologia》2006,44(5):718-730
To characterize the neural correlates of being personally involved in social interaction as opposed to being a passive observer of social interaction between others we performed an fMRI study in which participants were gazed at by virtual characters (ME) or observed them looking at someone else (OTHER). In dynamic animations virtual characters then showed socially relevant facial expressions as they would appear in greeting and approach situations (SOC) or arbitrary facial movements (ARB). Differential neural activity associated with ME>OTHER was located in anterior medial prefrontal cortex in contrast to the precuneus for OTHER>ME. Perception of socially relevant facial expressions (SOC>ARB) led to differentially increased neural activity in ventral medial prefrontal cortex. Perception of arbitrary facial movements (ARB>SOC) differentially activated the middle temporal gyrus. The results, thus, show that activation of medial prefrontal cortex underlies both the perception of social communication indicated by facial expressions and the feeling of personal involvement indicated by eye gaze. Our data also demonstrate that distinct regions of medial prefrontal cortex contribute differentially to social cognition: whereas the ventral medial prefrontal cortex is recruited during the analysis of social content as accessible in interactionally relevant mimic gestures, differential activation of a more dorsal part of medial prefrontal cortex subserves the detection of self-relevance and may thus establish an intersubjective context in which communicative signals are evaluated. 相似文献